7QDA

Crystal structure of CalpL

Summary for 7QDA

• Entry DOI: 10.2210/pdb7qda/pdb
• Descriptor: CalpL, SULFATE ION, TRIETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: protease, crispr type iii, coa, peptide binding protein
• Biological source: Sulfurihydrogenibium sp. YO3AOP1
• Total number of polymer chains: 1
• Total formula weight: 59647.49

Authors

Schneberger, N.,Hagelueken, G. (deposition date: 2021-11-26, release date: 2022-11-16, Last modification date: 2024-10-16)

Primary citation

Rouillon, C.,Schneberger, N.,Chi, H.,Blumenstock, K.,Da Vela, S.,Ackermann, K.,Moecking, J.,Peter, M.F.,Boenigk, W.,Seifert, R.,Bode, B.E.,Schmid-Burgk, J.L.,Svergun, D.,Geyer, M.,White, M.F.,Hagelueken, G.
Antiviral signalling by a cyclic nucleotide activated CRISPR protease.
Nature, 614:168-174, 2023

PubMed Abstract: CRISPR defence systems such as the well-known DNA-targeting Cas9 and the RNA-targeting type III systems are widespread in prokaryotes. The latter orchestrates a complex antiviral response that is initiated through the synthesis of cyclic oligoadenylates after recognition of foreign RNA. Among the large set of proteins that are linked to type III systems and predicted to bind cyclic oligoadenylates, a CRISPR-associated Lon protease (CalpL) stood out to us. CalpL contains a sensor domain of the SAVED family fused to a Lon protease effector domain. However, the mode of action of this effector is unknown. Here we report the structure and function of CalpL and show that this soluble protein forms a stable tripartite complex with two other proteins, CalpT and CalpS, that are encoded on the same operon. After activation by cyclic tetra-adenylate (cA), CalpL oligomerizes and specifically cleaves the MazF homologue CalpT, which releases the extracytoplasmic function σ factor CalpS from the complex. Our data provide a direct connection between CRISPR-based detection of foreign nucleic acids and transcriptional regulation. Furthermore, the presence of a SAVED domain that binds cyclic tetra-adenylate in a CRISPR effector reveals a link to the cyclic-oligonucleotide-based antiphage signalling system.

PubMed: 36423657
DOI: 10.1038/s41586-022-05571-7

Experimental method

X-RAY DIFFRACTION (2.1 Å)